Objective To investigate the effect of steroid therapy combined with different immunosuppressive agentsin the treatment of refractory nephrotic syndrome. Methods 70 patients of adult refractory nephrotic syndrome in our hospital from March 2016 to February 2019. 30 cases were divided into the observation group and 40 cases in the control group. Two groups were orally administered with methylprednisolone tablets. The observation group was given MMF treatment, and the control group was given FK506 capsules. The urine protein, serum index, treatment efficiency and adverse reactions were compared between the two groups. Results Three months after the treatment, compared with the control group, the difference of urine protein (1.2±0.4) g/D vs (2.8±0.5) g/D, serum albumin (42.6±2.7) g/L vs (33.6±2.5) g/L was significant (P＜0.05). IL 8 (53.21±6.72) μg/L vs (72.15±8.46) μ g/L was significantly lower (P＜0.05). The effective rate of treatment in the observation group (96.7%) was significantly higher than that in the control group (775%) (P＜0.05). The incidence of adverse reactions in the observation group (6.7%) was lower than that in the control group (10.0%), but the difference was not significant (P＞0.05). Conclusion Based on hormone therapy, mycophenolate mofetil ester can improve the urinary protein and serum protein index in adult refractory NS, and significantly reduce the serum SCR, bun, TGF-β1 and IL-8.